Mitochondrial Preservation in Celsior Versus Histidine Buffer Solution During Cardiac Ischemia and Reperfusion

Abstract

Various stressful conditions such as ischemia in cold cardioplegic solutions and reperfusion occur during heart transplantation. Since ATP production is essential for the maintenance of contractile activity, mitochondrial function may be a mediator of ischemia and ischemia/reperfusion (I/R) injury. We aimed at testing the ability of two distinct cardioplegic solutions, Celsior (Cs) and Histidine Buffer (HBS), to protect rat heart mitochondria (HM) function during ischemia alone or ischemia followed by reperfusion. A standard Krebs-Henseleit solution (KH) was used as "negative" control. Male and Female Wistar rats were divided into control (Ctrl), reperfusion control (Ctrl_R), ischemia and I/R groups. Ischemia and I/R were divided into three subgroups depending on the cardioplegic solution used (Cs, HBS or KH) and subjected to 4-or 6-h ischemia alone or followed by reperfusion. HM respiration and transmembrane electric potential (Deltapsi) were measured with oxygen and TPP(+)-selective electrodes, respectively. Mitochondrial electron microscopy and detection of protein carbonyl groups content were also performed. After ischemic heart preservation, mitochondrial respiration and Deltapsi were not significantly affected except for the respiratory control ratio (RCR). After I/R, state 3 respiration, RCR and Deltapsi were decreased, especially in HM from male and for complex I substrates (CxI). HM preserved in HBS had less membrane disruption, segregation or disintegration. We conclude that (a) female HM were less sensitive to I/R, (b) CxI was particularly affected by I/R, (c) two cardioplegic solutions tested act in different mitochondrial targets preventing mitochondrial collapse.

Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender

“…In our previous studies, we have concluded that hearts from females are less sensitive to oxidative stress in I/R conditions (16). Clinically, women are known to have less mortality resulting from coronary heart disease than men (33); accordingly, estrogen treatment increases superoxide dismutase (34) and decreases oxidative damage (35).…”

“…The ischemia protocol was performed according to previously described procedures (15,16). Briefly, after intraperitoneal anesthesia using ketamine (50 mg/kg) plus largactil (10 mg/kg), animals were sacrificed and an incision was made in the abdominal area.…”

Increased Abdominal Adiposity Exacerbates Ex-Vivo Cardiac Reperfusion Injury through Augmented Mitochondrial Oxidative Stress

“…In the reperfused myocardium, excess calcium invades the mitochondria [35] and triggers noticeable ROS production [36]. ROS inhibit the aconitase enzyme within the Krebs cycle [37], which blocks ATP synthesis and triggers the functional abnormalities that characterize reperfusion [38]. Obesity may modulate mitochondrial ROS production and the recovery of cardiac functional activity during reperfusion.…”

Anti-apoptotic protection afforded by cardioplegic celsior and histidine buffer solutions to hearts subjected to ischemia and ischemia/reperfusion

“…We have described in previous studies [Alves et al, 2009, 2011a] the mitochondrial protection afforded by both Celsior (Cs) and Histidine buffer (HBS), as well as how both solutions regulate substrate preference during I/R. In both studies, it was concluded that HBS proved to be a good alternative to Cs.…”

“…The aim of the present work was to compare the protection afforded by two cardioplegic solutions: the worldwide clinically used Cs, and an emerging solution in clinical and experimental research, HBS [Takeuchi et al, 1999a,b; Alves et al, 2009], against several apoptotic signaling events in hearts subjected to ischemia alone and I/R. Two distinct preservation periods were investigated to compare the effect of moderate (4 h) versus severe ischemia (6 h).…”